David Young - Academia.edu (original) (raw)

Papers by David Young

Research paper thumbnail of Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins update

Pediatric Pulmonology, Jun 7, 2017

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and ... more Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an overview of the classes of intravenous anti-pseudomonal antibiotics, the findings of anti-pseudomonal antibiotic utilization surveys, the current antibiotic dosing recommendations from the U.S. and Europe, and the pharmacokinetic (PK) and pharmacodynamic (PD) differences between CF and non-CF individuals. Anti-pseudomonal antibiotic classes include beta-lactams, aminoglycosides, fluoroquinolones, and colistimethate sodium. Recent surveys of antibiotic utilization in CF Foundation-accredited care centers have shown that a large number of centers are not following recommended dosing strategies despite published recommendations in the U.S. and Europe. The recommended doses for anti-pseudomonal antibiotics may be higher than FDA-approved doses due to PK and PD differences. As a large portion of CF patients will not regain their lung function following an APE, it seems possible that currently available antipseudomonal agents are being used sub-optimally. As new anti-pseudomonal agents are not currently available, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat pulmonary exacerbations in an effort to improve outcomes for CF patients infected with Pseudomonas aeruginosa.

Research paper thumbnail of Effective pharmacy provider handoff communication for transition of patient care in CF

Pediatric Pulmonology, May 8, 2023

Research paper thumbnail of The indispensable role of pharmacy services and medication therapy management in cystic fibrosis

Pediatric Pulmonology, Aug 11, 2021

Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary ap... more Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)‐specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate, and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF‐specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF.

Research paper thumbnail of State of the art in cystic fibrosis pharmacology optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: III. Executive summary

Pediatric Pulmonology, Mar 15, 2021

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated... more Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Research paper thumbnail of A Pharmacokinetic Evaluation of Tobramycin Administered One, Two, and Three Times Daily to Children with Cystic Fibrosis

Research paper thumbnail of Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: II. Therapies for allergic bronchopulmonary aspergillosis

Pediatric Pulmonology, Sep 29, 2020

This review is the second article in the State‐of‐the‐Art series and aims to evaluate medications... more This review is the second article in the State‐of‐the‐Art series and aims to evaluate medications used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in pediatric and adult patients with cystic fibrosis (CF). ABPA is one of several organisms that are found in the airways of CF patients. This review provides an evidence‐based summary of pharmacokinetic (PK)/pharmacodynamic (PD), tolerability, and efficacy studies of medications including corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, and voriconazole), and a monoclonal antibody omalizumab in the treatment of ABPA and identifies areas where further study is warranted.

Research paper thumbnail of State of the art in cystic fibrosis pharmacology—Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: I. Anti‐methicillin‐resistant <i>Staphylococcus aureus</i> (MRSA) antibiotics

Pediatric Pulmonology, Oct 14, 2019

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated... more Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Research paper thumbnail of Patient Perspectives on the Use of Digital Technology to Help Manage Cystic Fibrosis

Background Digital Health Technologies (DHTs) have shown potential to improve health outcomes thr... more Background Digital Health Technologies (DHTs) have shown potential to improve health outcomes through improved medication adherence in different disease states1,2. Cystic Fibrosis (CF) requires care coordination across pharmacies, patients, and providers3,4. DHTs can potentially support patients, providers, and pharmacists in diseases like CF, where high medication burden can negatively impact patient quality of life and outcomes. Methods In this prospective cohort study, a CF-specific mobile application (Phlo) was distributed to adults with CF who received care at the University of Utah Cystic Fibrosis Center, used an iPhone, and filled prescriptions through the University of Utah Specialty Pharmacy services. Participants were asked to use Phlo for 90 days with an optional 90-day extension period. Participants completed four surveys at baseline and after 90 days. Changes in patient-reported outcomes, adherence, clinical outcomes, and healthcare resource utilization from baseline to...

Research paper thumbnail of Population Pharmacokinetics of Vancomycin Used in the Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

Research paper thumbnail of Understanding the expanding role of pharmacy services in outpatient cystic fibrosis care

Pediatric Pulmonology, 2021

Cystic fibrosis (CF) patients utilize an average of 10 (±5) medications per day. Given the comple... more Cystic fibrosis (CF) patients utilize an average of 10 (±5) medications per day. Given the complexity of the medication regimen, the CF Foundation (CFF) recommends pharmacists as members of the CF care team. The areas of pharmacy services have been identified in the literature. “Limited access pharmacists” are consulted to answer questions, assist in evaluating serum drug concentrations, provide medication education, and monitor for drug‐drug interactions. Reduction in hospital length of stay has been shown through this collaboration. “Full access pharmacists” provide comprehensive medication therapy management resulting in medication adherence and access improvements, sustainability of treatments, improved provider communication, reduced medication errors and costs, expedited medication refill authorization, increased utilization of respiratory therapists, enhanced discussion of medications with CF team members, and reduction in the number of pharmacies utilized by patients to fill CF medications. An integrated CF pharmacy team are essential members of the multidisciplinary CF care team that have been shown to improve in CF medication access, increases in body weight and body mass index, reduction in prior authorization submission times, reduction in medication delivery times, expedited medication refill authorizations, increased collaboration with respiratory therapists, augmented discussion of medication with CF team members, and reduction in the number of pharmacies utilized by CF patients. There is a need to further evaluate the impact of outpatient CF pharmacy services due to the improvements in the care on patients and families affected by CF, and as the number of CFF‐accredited care centers integrates CF pharmacy teams throughout the country increases.

Research paper thumbnail of An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin-Resistant Staphylococcus aureus

Journal of clinical pharmacology, Jan 29, 2018

The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients wi... more The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations-a postdistributive and a trough-are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation-based 2-point monitoring approach. AUCs were either obtained from a single trough concentration-fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify t...

Research paper thumbnail of Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Antimicrobial agents and chemotherapy, 2018

Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharma... more Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimatio...

Research paper thumbnail of Pharmacokinetics of Continuous Infusion Beta-Lactams in the Treatment of Acute Pulmonary Exacerbations in Adult Cystic Fibrosis Patients

Chest, Jan 13, 2018

Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (B... more Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (BL) antibiotics in cystic fibrosis (CF) patients; however, little is known regarding pharmacokinetic changes during treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. This study is a retrospective cohort study of 162 adult CF patients admitted to the University of Utah Hospital between January 1, 2008 and May 15, 2014 for treatment of an APE with both a CI BL and intravenous tobramycin. We extracted the administered doses of CI BL and tobramycin along with serum drug concentrations and calculated medication clearance rates. The primary outcome was change in clearance rates of CI BL between day 2 and day 7 of APE treatment. BL clearance rate increased 20.7% (95% CI, 11.42 - 32.49; p<0.001), whereas tobramycin clearance rate decreased 6.3% (95% CI, -12.29 - -4.45; p<0.001). Th...

Research paper thumbnail of Improving performance in the detection and management of cystic fibrosis-related diabetes in the Mountain West Cystic Fibrosis Consortium

BMJ open diabetes research & care, 2016

Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality... more Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality. Improved detection and management may improve outcomes; however, actual practice falls short of published guidelines. We studied efforts to improve CFRD screening and management in the Mountain West CF Consortium (MWCFC). This is a prospective observational cohort study evaluating quality improvement by accredited CF centers in Arizona, Colorado, New Mexico, and Utah performed between 2002 and 2008. After Institutional Review Board (IRB) approval, centers evaluated adherence with CF Foundation guidelines for CFRD. Each center developed and implemented quality improvement plans to improve both screening and management. Centers were reassessed 1 year later. Initially, each CF center had low adherence with screening recommendations (26.5% of eligible patients) that did not improve during the study. However, patients with confirmed CFRD markedly increased (141 (12% of MWCFC patients) to 22...

Research paper thumbnail of A survey of the utilization of anti-pseudomonal beta-lactam therapy in cystic fibrosis patients

Pediatric pulmonology, 2011

The purpose of this study was to characterize the utilization of anti-pseudomonal beta-lactam ant... more The purpose of this study was to characterize the utilization of anti-pseudomonal beta-lactam antibiotics in the treatment of acute pulmonary exacerbations (APE) among Cystic Fibrosis Foundation (CFF)-accredited care centers. An anonymous national cross-sectional survey of CFF-accredited care centers was performed using an electronic survey tool (SurveyMonkey.com®). One hundred and twenty-one of 261 centers completed the survey (46%) representing 56% (14,856/26,740) of patients in the CFF Patient Registry. One hundred and nineteen of 121 (98%) respondents reported using beta-lactams for the treatment of APE. Intermittent dosing regimens constituted 155/167 (93%) reported regimens, while extended infusions were 12/167 (7%). Ceftazidime was the most commonly utilized beta-lactam comprising 74/167 (44%) of all infusions (intermittent and extended) of which 70/74 (95%) were intermittent infusions. The majority of intermittent ceftazidime regimens (56/70; 80%) were at doses lower than CF...

Research paper thumbnail of Population pharmacokinetics of intermittent vancomycin in children with cystic fibrosis

Research paper thumbnail of Utilization of antibiotics for methicillin-resistant Staphylococcus aureus infection in cystic fibrosis

Pediatric pulmonology, Jan 5, 2015

The purpose of this study was to characterize the utilization of antibiotics for chronic methicil... more The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx). An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool. Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in bot...

Research paper thumbnail of Continuous infusion meropenem and ticarcillin-clavulanate in pediatric cystic fibrosis patients

Pediatric Pulmonology, 2013

Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been... more Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been previously reported to be administered by continuous infusion (CI) in pediatric CF patients. We present two cases administering intravenous (IV) meropenem and ticarcillinclavulanate by CI in pediatric CF patients. The delivery of beta-lactam antibiotics via CI should be considered in order to optimize the pharmacodynamics (PD) of beta-lactams in the treatment of acute pulmonary exacerbations (APE).

Research paper thumbnail of The Use of Doripenem in Pediatric Cystic Fibrosis Patients in Case of Meropenem Shortages

Pediatric Pulmonology, 2013

Ceftazidime is the only anti‐pseduomonal beta‐lactam that has been reported to be administered by... more Ceftazidime is the only anti‐pseduomonal beta‐lactam that has been reported to be administered by extended infusion in pediatric cystic fibrosis (CF) patients. A small pediatric pharmacokinetic/pharmacodynamic study has been published regarding the use of intermittent extended infusion doripenem in the treatment of an acute pulmonary exacerbation (APE) in pediatric CF patients; however, clinical use of intermittent extended infusion doripenem in pediatric CF patients has not been previously reported. We present three cases administering intermittent extended infusion doripenem in pediatric CF patients for the treatment of an APE in the case of replacing meropenem due to shortage. The delivery of beta‐lactam antibiotics via intermittent extended infusion should be considered in order to optimize the pharmacodynamics of beta‐lactams in the treatment of an APE. Pediatr Pulmonol. 2014; 49:E48–E51. © 2013 Wiley Periodicals, Inc.

Research paper thumbnail of Intermittent and extended-infusion Beta-Lactam utilization in cystic fibrosis

Pediatric Pulmonology, 2012

We are writing in this letter in response to interest from the cystic fibrosis (CF) community reg... more We are writing in this letter in response to interest from the cystic fibrosis (CF) community regarding the article ''A Survey of the Utilization of Anti-Pseudomonal Beta-Lactam Therapy in Cystic Fibrosis Patients'' by Zobell et al. 1 The interest surrounds the information that was published about the utilization of intermittent and extended-infusion beta-lactam therapy. The published utilization rate of intermittent and extended infusion beta-lactams were 155/167 (93%) and 12/167 (7%) of survey respondents from Cystic Fibrosis Foundation (CFF)-accredited care centers, respectively. 1 However, the dosing regimens utilized were not reported. We would like to take this opportunity to report those data at this time. The most commonly utilized intermittent (i.e., over 30 min) anti-pseudomonal beta-lactam was ceftazidime (70/155, 45%). 1 The utilization rates for the other antibiotics were piperacillin-tazobactam (32/155, 21%), cefepime (23/155, 15%), meropenem (20/155, 13%), ticarcillin-clavulanate (8/155, 5%), and aztreonam (2/ 155, 1%). 1 Of the 12 respondents who utilize extendedinfusion (i.e., over 4 hr or continuously) beta-lactams routinely in the treatment of acute pulmonary exacerbations (APE), the commonly utilized antibiotic was ceftazidime (4/12, 33%). 1 Other reported antibiotics utilized by extended infusion were cefepime (3/12,

Research paper thumbnail of Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins update

Pediatric Pulmonology, Jun 7, 2017

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and ... more Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an overview of the classes of intravenous anti-pseudomonal antibiotics, the findings of anti-pseudomonal antibiotic utilization surveys, the current antibiotic dosing recommendations from the U.S. and Europe, and the pharmacokinetic (PK) and pharmacodynamic (PD) differences between CF and non-CF individuals. Anti-pseudomonal antibiotic classes include beta-lactams, aminoglycosides, fluoroquinolones, and colistimethate sodium. Recent surveys of antibiotic utilization in CF Foundation-accredited care centers have shown that a large number of centers are not following recommended dosing strategies despite published recommendations in the U.S. and Europe. The recommended doses for anti-pseudomonal antibiotics may be higher than FDA-approved doses due to PK and PD differences. As a large portion of CF patients will not regain their lung function following an APE, it seems possible that currently available antipseudomonal agents are being used sub-optimally. As new anti-pseudomonal agents are not currently available, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat pulmonary exacerbations in an effort to improve outcomes for CF patients infected with Pseudomonas aeruginosa.

Research paper thumbnail of Effective pharmacy provider handoff communication for transition of patient care in CF

Pediatric Pulmonology, May 8, 2023

Research paper thumbnail of The indispensable role of pharmacy services and medication therapy management in cystic fibrosis

Pediatric Pulmonology, Aug 11, 2021

Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary ap... more Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)‐specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate, and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF‐specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF.

Research paper thumbnail of State of the art in cystic fibrosis pharmacology optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: III. Executive summary

Pediatric Pulmonology, Mar 15, 2021

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated... more Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Research paper thumbnail of A Pharmacokinetic Evaluation of Tobramycin Administered One, Two, and Three Times Daily to Children with Cystic Fibrosis

Research paper thumbnail of Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: II. Therapies for allergic bronchopulmonary aspergillosis

Pediatric Pulmonology, Sep 29, 2020

This review is the second article in the State‐of‐the‐Art series and aims to evaluate medications... more This review is the second article in the State‐of‐the‐Art series and aims to evaluate medications used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in pediatric and adult patients with cystic fibrosis (CF). ABPA is one of several organisms that are found in the airways of CF patients. This review provides an evidence‐based summary of pharmacokinetic (PK)/pharmacodynamic (PD), tolerability, and efficacy studies of medications including corticosteroids, amphotericin B, azole antifungals (isavuconazole, itraconazole, posaconazole, and voriconazole), and a monoclonal antibody omalizumab in the treatment of ABPA and identifies areas where further study is warranted.

Research paper thumbnail of State of the art in cystic fibrosis pharmacology—Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: I. Anti‐methicillin‐resistant <i>Staphylococcus aureus</i> (MRSA) antibiotics

Pediatric Pulmonology, Oct 14, 2019

Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated... more Acute pulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Research paper thumbnail of Patient Perspectives on the Use of Digital Technology to Help Manage Cystic Fibrosis

Background Digital Health Technologies (DHTs) have shown potential to improve health outcomes thr... more Background Digital Health Technologies (DHTs) have shown potential to improve health outcomes through improved medication adherence in different disease states1,2. Cystic Fibrosis (CF) requires care coordination across pharmacies, patients, and providers3,4. DHTs can potentially support patients, providers, and pharmacists in diseases like CF, where high medication burden can negatively impact patient quality of life and outcomes. Methods In this prospective cohort study, a CF-specific mobile application (Phlo) was distributed to adults with CF who received care at the University of Utah Cystic Fibrosis Center, used an iPhone, and filled prescriptions through the University of Utah Specialty Pharmacy services. Participants were asked to use Phlo for 90 days with an optional 90-day extension period. Participants completed four surveys at baseline and after 90 days. Changes in patient-reported outcomes, adherence, clinical outcomes, and healthcare resource utilization from baseline to...

Research paper thumbnail of Population Pharmacokinetics of Vancomycin Used in the Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

Research paper thumbnail of Understanding the expanding role of pharmacy services in outpatient cystic fibrosis care

Pediatric Pulmonology, 2021

Cystic fibrosis (CF) patients utilize an average of 10 (±5) medications per day. Given the comple... more Cystic fibrosis (CF) patients utilize an average of 10 (±5) medications per day. Given the complexity of the medication regimen, the CF Foundation (CFF) recommends pharmacists as members of the CF care team. The areas of pharmacy services have been identified in the literature. “Limited access pharmacists” are consulted to answer questions, assist in evaluating serum drug concentrations, provide medication education, and monitor for drug‐drug interactions. Reduction in hospital length of stay has been shown through this collaboration. “Full access pharmacists” provide comprehensive medication therapy management resulting in medication adherence and access improvements, sustainability of treatments, improved provider communication, reduced medication errors and costs, expedited medication refill authorization, increased utilization of respiratory therapists, enhanced discussion of medications with CF team members, and reduction in the number of pharmacies utilized by patients to fill CF medications. An integrated CF pharmacy team are essential members of the multidisciplinary CF care team that have been shown to improve in CF medication access, increases in body weight and body mass index, reduction in prior authorization submission times, reduction in medication delivery times, expedited medication refill authorizations, increased collaboration with respiratory therapists, augmented discussion of medication with CF team members, and reduction in the number of pharmacies utilized by CF patients. There is a need to further evaluate the impact of outpatient CF pharmacy services due to the improvements in the care on patients and families affected by CF, and as the number of CFF‐accredited care centers integrates CF pharmacy teams throughout the country increases.

Research paper thumbnail of An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin-Resistant Staphylococcus aureus

Journal of clinical pharmacology, Jan 29, 2018

The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients wi... more The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations-a postdistributive and a trough-are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation-based 2-point monitoring approach. AUCs were either obtained from a single trough concentration-fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify t...

Research paper thumbnail of Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

Antimicrobial agents and chemotherapy, 2018

Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharma... more Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimatio...

Research paper thumbnail of Pharmacokinetics of Continuous Infusion Beta-Lactams in the Treatment of Acute Pulmonary Exacerbations in Adult Cystic Fibrosis Patients

Chest, Jan 13, 2018

Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (B... more Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (BL) antibiotics in cystic fibrosis (CF) patients; however, little is known regarding pharmacokinetic changes during treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. This study is a retrospective cohort study of 162 adult CF patients admitted to the University of Utah Hospital between January 1, 2008 and May 15, 2014 for treatment of an APE with both a CI BL and intravenous tobramycin. We extracted the administered doses of CI BL and tobramycin along with serum drug concentrations and calculated medication clearance rates. The primary outcome was change in clearance rates of CI BL between day 2 and day 7 of APE treatment. BL clearance rate increased 20.7% (95% CI, 11.42 - 32.49; p<0.001), whereas tobramycin clearance rate decreased 6.3% (95% CI, -12.29 - -4.45; p<0.001). Th...

Research paper thumbnail of Improving performance in the detection and management of cystic fibrosis-related diabetes in the Mountain West Cystic Fibrosis Consortium

BMJ open diabetes research & care, 2016

Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality... more Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality. Improved detection and management may improve outcomes; however, actual practice falls short of published guidelines. We studied efforts to improve CFRD screening and management in the Mountain West CF Consortium (MWCFC). This is a prospective observational cohort study evaluating quality improvement by accredited CF centers in Arizona, Colorado, New Mexico, and Utah performed between 2002 and 2008. After Institutional Review Board (IRB) approval, centers evaluated adherence with CF Foundation guidelines for CFRD. Each center developed and implemented quality improvement plans to improve both screening and management. Centers were reassessed 1 year later. Initially, each CF center had low adherence with screening recommendations (26.5% of eligible patients) that did not improve during the study. However, patients with confirmed CFRD markedly increased (141 (12% of MWCFC patients) to 22...

Research paper thumbnail of A survey of the utilization of anti-pseudomonal beta-lactam therapy in cystic fibrosis patients

Pediatric pulmonology, 2011

The purpose of this study was to characterize the utilization of anti-pseudomonal beta-lactam ant... more The purpose of this study was to characterize the utilization of anti-pseudomonal beta-lactam antibiotics in the treatment of acute pulmonary exacerbations (APE) among Cystic Fibrosis Foundation (CFF)-accredited care centers. An anonymous national cross-sectional survey of CFF-accredited care centers was performed using an electronic survey tool (SurveyMonkey.com®). One hundred and twenty-one of 261 centers completed the survey (46%) representing 56% (14,856/26,740) of patients in the CFF Patient Registry. One hundred and nineteen of 121 (98%) respondents reported using beta-lactams for the treatment of APE. Intermittent dosing regimens constituted 155/167 (93%) reported regimens, while extended infusions were 12/167 (7%). Ceftazidime was the most commonly utilized beta-lactam comprising 74/167 (44%) of all infusions (intermittent and extended) of which 70/74 (95%) were intermittent infusions. The majority of intermittent ceftazidime regimens (56/70; 80%) were at doses lower than CF...

Research paper thumbnail of Population pharmacokinetics of intermittent vancomycin in children with cystic fibrosis

Research paper thumbnail of Utilization of antibiotics for methicillin-resistant Staphylococcus aureus infection in cystic fibrosis

Pediatric pulmonology, Jan 5, 2015

The purpose of this study was to characterize the utilization of antibiotics for chronic methicil... more The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx). An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool. Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in bot...

Research paper thumbnail of Continuous infusion meropenem and ticarcillin-clavulanate in pediatric cystic fibrosis patients

Pediatric Pulmonology, 2013

Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been... more Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been previously reported to be administered by continuous infusion (CI) in pediatric CF patients. We present two cases administering intravenous (IV) meropenem and ticarcillinclavulanate by CI in pediatric CF patients. The delivery of beta-lactam antibiotics via CI should be considered in order to optimize the pharmacodynamics (PD) of beta-lactams in the treatment of acute pulmonary exacerbations (APE).

Research paper thumbnail of The Use of Doripenem in Pediatric Cystic Fibrosis Patients in Case of Meropenem Shortages

Pediatric Pulmonology, 2013

Ceftazidime is the only anti‐pseduomonal beta‐lactam that has been reported to be administered by... more Ceftazidime is the only anti‐pseduomonal beta‐lactam that has been reported to be administered by extended infusion in pediatric cystic fibrosis (CF) patients. A small pediatric pharmacokinetic/pharmacodynamic study has been published regarding the use of intermittent extended infusion doripenem in the treatment of an acute pulmonary exacerbation (APE) in pediatric CF patients; however, clinical use of intermittent extended infusion doripenem in pediatric CF patients has not been previously reported. We present three cases administering intermittent extended infusion doripenem in pediatric CF patients for the treatment of an APE in the case of replacing meropenem due to shortage. The delivery of beta‐lactam antibiotics via intermittent extended infusion should be considered in order to optimize the pharmacodynamics of beta‐lactams in the treatment of an APE. Pediatr Pulmonol. 2014; 49:E48–E51. © 2013 Wiley Periodicals, Inc.

Research paper thumbnail of Intermittent and extended-infusion Beta-Lactam utilization in cystic fibrosis

Pediatric Pulmonology, 2012

We are writing in this letter in response to interest from the cystic fibrosis (CF) community reg... more We are writing in this letter in response to interest from the cystic fibrosis (CF) community regarding the article ''A Survey of the Utilization of Anti-Pseudomonal Beta-Lactam Therapy in Cystic Fibrosis Patients'' by Zobell et al. 1 The interest surrounds the information that was published about the utilization of intermittent and extended-infusion beta-lactam therapy. The published utilization rate of intermittent and extended infusion beta-lactams were 155/167 (93%) and 12/167 (7%) of survey respondents from Cystic Fibrosis Foundation (CFF)-accredited care centers, respectively. 1 However, the dosing regimens utilized were not reported. We would like to take this opportunity to report those data at this time. The most commonly utilized intermittent (i.e., over 30 min) anti-pseudomonal beta-lactam was ceftazidime (70/155, 45%). 1 The utilization rates for the other antibiotics were piperacillin-tazobactam (32/155, 21%), cefepime (23/155, 15%), meropenem (20/155, 13%), ticarcillin-clavulanate (8/155, 5%), and aztreonam (2/ 155, 1%). 1 Of the 12 respondents who utilize extendedinfusion (i.e., over 4 hr or continuously) beta-lactams routinely in the treatment of acute pulmonary exacerbations (APE), the commonly utilized antibiotic was ceftazidime (4/12, 33%). 1 Other reported antibiotics utilized by extended infusion were cefepime (3/12,